Nucleic Acids Research Advance Access originally published online on March 10, 2009
Nucleic Acids Research 2009 37(8):2747-2756; doi:10.1093/nar/gkp121
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Nucleic Acids Research, 2009, Vol. 37, No. 8 2747-2756
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Regulatory targets of quorum sensing in Vibrio cholerae: evidence for two distinct HapR-binding motifs
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA, 2Department of Microbiology, MOA Key Lab of Microbiological Engineering of Agricultural Environment, Nanjing Agricultural University, Nanjing, China and 3Department of Physics, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
*To whom correspondence should be addressed. Tel: +1 215 573 4104. Fax: +1 215898 9557; Email: junzhu{at}mail.med.upenn.edu
Received November 10, 2008. Revised February 13, 2009. Accepted February 13, 2009.
The quorum-sensing pathway in Vibrio cholerae controls the expression of the master regulator HapR, which in turn regulates several important processes such as virulence factor production and biofilm formation. While HapR is known to control several important phenotypes, there are only a few target genes known to be transcriptionally regulated by HapR. In this work, we combine bioinformatic analysis with experimental validation to discover a set of novel direct targets of HapR. Our results provide evidence for two distinct binding motifs for HapR-regulated genes in V. cholerae. The first binding motif is similar to the motifs recently discovered for orthologs of HapR in V. harveyi and V. vulnificus. However, our results demonstrate that this binding motif can be of variable length in V. cholerae. The second binding motif shares common elements with the first motif, but is of fixed length and lacks dyad symmetry at the ends. The contributions of different bases to HapR binding for this second motif were demonstrated using systematic mutagenesis experiments. The current analysis presents an approach for systematically expanding our knowledge of the quorum-sensing regulon in V. cholerae and other related bacteria.